The clinical complications of diabetes manifest themselves in both skeletal and nonskeletal connective tissues. Despite the extensive literature relating to the complications observed for non-skeletal tissues in diabetes, the metabolic changes occurring in bone and cartilage have received little attention. Preliminary studies suggest that in diabetes the cartilage undergoes morphological and metabolic changes similar to those observed in degenerative joint disease. However, the biochemistry of the cartilage proteoglycans in diabetes has not been studied. In this study, it is proposed to examine the chemical and physical characteristics of proteoglycans obtained from articular cartilage of rats with streptozotocin-induced diabetes. Articular cartilage proteoglycans will be isolated by established methods and their chemical and physical properties determined i.e., chemical composition, the presence of large molecular weight aggregates, the molecular size of the proteoglycan monomers and their ability to bind hyaluronic acid, the molecular size of the constituent glycosaminoglycan chains. In addition, the various proteoglycan preparations will be examined, both qualitatively and quantitatively for the presence of the link proteins and proteoglycan monomer using specific radioimmunoassay procedures. Furthermore, transplanted Swarm rat chondrosarcoma in streptozotocin-induced diabetic rats will be used: (1) to obtain large amounts of material for more detailed physical and chemical characterization of the proteoglycan monomer, hyaluronic acid and link protein in diabetes and (2) as a means of studying metabolic changes in the cartilage proteoglycan without the mechanical influences of pressure and friction which are normally experienced in the diarthrodal joint. By these means it will be possible to determine if there are chemical and structural differences in the composition of cartilage proteoglycans in diabetes and whether these changes are similar to those observed in degenerative joint diseases. Any changes found may be common to proteoglycans of other connective tissues such as cardiovascular tissue. These changes may contribute significantly to the cardiovascular complications which become evident in the later stages of diabetes.